CHOLINERGIC MECHANISMS Phylogenetic Aspects, Central and Peripheral Synapses, and Clinical Significance
ADVANCES IN BEHAVIORAL BIOLOGY
Editorial Board:
Jan Bures Irwin Kopin Bruce McEwen James McGaugh
Institute of Physiology, Prague, Czechoslovakia National Institute of Mental Health, Bethesda, Maryland Rockefeller University, New York, New York University of California, Irvine, California
Karl Pribram Jay Rosenblatt Lawrence Weiskrantz
Stanford University School of Medicine, Stanford, California Rutgers University, Newark, New Jersey University of Oxford, Oxford, England
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CHOLINERGIC MECHANISMS Phylogenetic Aspects, Central and Peripheral Synapses, and Clinical Significance
Edited by
Giancarlo Pepeu Institute of Pharmacology University of Florence Florence, Italy
and
Herbert Ladinsky Mario Negri Institute for Pharmacological Research Milan, Italy
PLENUM PRESS • NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Main entry under title:
Cholinergic Mechanisms: Phylogenetic Aspects, Central and Peripheral Synapses, and Clinical Significance.
Proceedings of the International Symposium on Cholinergic Mechanisms: Phylogenetic Aspects, Central and Peripheral Synapses, and Clinical Significance, held Mar. 11-15, 1980, in Florence, Italy.
Includes bibliographies and indexes. 1. Acetylcholine - Metabolism - Congresses. 2. Cholinergic receptors - Con
gresses. 3. Synapses-Congresses. 4. Parasympathomimetic agents- TestingCongresses. I. Pepeu, Ginacarlo. 11. Ladinsky, Herbert. 111. International Symposium on Cholinergic Mechanisms: Phylogenetic Aspects, Central and Peripheral Synapses, and Clinical Significance (1980 : Florence, Italy) IDNLM: 1. Acetylcholine-Congresses. QV 122 161c 19801 QP921.A25C48 612.8042 81-11936
Proceedings of an International Symposium on Cholinergic Mechanisms: Phylogenetic Aspects, Central and Peripheral Synapses, and Clinical Significance, held March 11-15, 1980, in Florence, Italy
© 1981 Plenum Press, New York Softcover reprint of the hardcover 1 st edition 1981
A Division of Plenum Publishing Corporation 233 Spring Street, New York, N.Y. 10013
All rights reserved
AACR2
No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission trom the publisher
ISBN 978-1-4684-8645-2 ISBN 978-1-4684-8643-8 (eBook)DOI 10.1007/978-1-4684-8643-8
SPONSORED BY
Societa Italiana di Farmacologia
International Union Pharmacology (IUPHAR)
Consiglio Nazionale delle Ricerche
ACKNOWLEDGMENT
The Symposium has been made possible by a
grant from the Consiglio Nazionale delle
Ricerche and by the generous support of
Fidia Research Laboratoreis, Abano Terme
(Padua) Italy.
ORGANIZING COMMITTEE
Lorenzo Beani Department of Pharmacology University of Ferrara Ferrara, Italy
Edith Heilbronn Unit of Neurochemistry and
Neurotoxicology University of Stockholm Stockholm, Sweden
Donald J. Jenden Department of Pharmacology School of Medicine University of California Los Angeles, California
Alexander Karczmar Department of Pharmacology Stritch School of Medicine Loyola University Maywood, Illinois
vi
Herbert Ladinsky The Mario Negri Institute for Pharmacological Research Milan, Italy
Peter G. Waser Institute of Pharmacology University of Zurich Zurich, Switzerland
Victor P. Whittaker Max-Planck Institut for Biomedical Research Gottingen, FR Germany
Giancar10 Pepeu, Chairman Department of Pharmacology University of Florence Florence, Italy
PREFACE
Every three years early Spring witnesses the convening of a small group of neuroscientists from many parts of the world. They are devoted to the study of acetylcholine, the oldest of the known neurotransmitters. To assess the level of knowledge, to take stock of the still unsolved problems, to evaluate the practical meaning of their findings, the cholinologists first met in 1969 in the eerie atmosphere of a snow-covered Swedish forest, the second in the Swiss Alps, the third facing the surf and foam of the Pacific waves. Finally in March 1980 Florence, her trees burgeoning in the mild rain of March, confronted them with the temptation of her monuments and museums. But the cholinologists bravely dismissed the temptations and went on with the presentations and discussions of the many papers which form the present book.
The papers describe the most recent development of investigations on acetylcholine. They open with an extensive coverage of the developmental and phylogenetic aspects of the cholinergic neurons. The regulation of acetylcholine synthesis, release, postsynaptic, electrical and trophic effects in the peripheral cholinergic synapses including ganglia, neuromuscular junction, myentheric plexus and heart is then covered. Special emphasis is given to the cholinergic mechanisms in the eye. But the largest part of the papers are devoted to the central cholinergic synapse, to the possibility of influencing its function through drugs and precursors and to the clinical meaning of the most recent findings in this realm. The fast moving knowledge on the central cholinergic receptors, the elusive central cholinergic pathways, the complex interactions between acetylcholine and other neurotransmitter systems also are the topic of several pages.
Many young scientists have joined in recent years the cholinergic field and to them was given the opportunity to present their work together with that of many old hands in this business. The book is a blend of basic and clinically oriented papers and should therefore be a useful source of ideas, techniques and references for biochemists, physiologists, pharmacologists and neuropsychiatristi.
viii PREFACE
We would like to express our gratitude to the members of the Scientific Committee and particularly to Dr. Whittaker, who gave valuable suggestions for the choice of the participants and the arrangement of the program, to the local committee to whom the participants owe the perfect organization of the meeting.
We are particularly grateful to Mrs. Flo Comes for her unique expertise and patience in editing the manuscripts and preparing them in the final form.
Last but not least we want to acknowledge the generous financial support of the Consiglio Nazionale delle Ricerche and of Fidia Research Laboratories which made the meeting possible.
Giancarlo Pepeu Florence
November 1980
Herbert Ladinsky Milan
CONTENTS
DEVELOPMENTAL AND PHYLOGENETIC ASPECTS OF THE CHOLINERGIC NEURONE
ACETYLCHOLINE BIOSYNTHESIS IN DEVELOPING CHOLINERGIC SYNAPSES
E. Giacobini & M. Marchi
AGING OF CHOLINERGIC SYNAPSES IN THE PERIPHERAL AUTONOMIC NERVOUS SYSTEM
M. Marchi & E. Giacobini
THE CHEMICAL EMBRYOLOGY OF THE ELECTROMOTOR SYSTEM OF TORPEDO MARMORATA
W.D. Krenz, T. Tashiro, K. Wachtler, V.P. Whittaker & V. Witzmann
THE REGIONAL DISTRIBUTION OF ACETYLCHOLINE,CHOLINACETYLTRANSFERASE, AND ACETYLCHOLINESTERASE IN VERTEBRATE BRAINS OF DIFFERENT PHYLOGENETIC LEVELS
K. Wachtler
CHOLINE UPTAKE AND CHOLINE ACETYL TRANSFERASE IN BRAIN OF DEVELOPING RATS MADE HYPOTHYROID WITH PROPYLTHIOURACIL
R.N. Kalaria, A.M. Kotas, A.K. Prince, R. Reynolds
1
25
47
59
& P.T.H. Wong 73
MORPHOLOGICAL ANALYSIS OF CHICK EMBRYO HEART DEVELOPMENT
L. Sisto-Daneo & G. Filogamo
ix
85
x
PLACENTAL CHOLINE ACETYLTRANSFERASE PURIFICATION AND PROPERTIES
C. Froissart & R. Massare11i
CONTENTS
91
PERIPHERAL CHOLINERGIC SYNAPSES: GANGLIA
THE RELATIONSHIP BETWEEN CHOLINE UPTAKE AND ACETYLCHOLINE SYNTHESIS IN A SYMPATHETIC GANGLION
B. Collier & S. 0' Regan
MULTIPLE MECHANISMS IN GANGLIONIC TRANSMISSION
N.J. Dun & A.G. Karczmar
PGE1-INDUCED cAMP BIOSYNTHESIS IN THE SUPERIOR CERVICAL GANGLION OF DIFFERENT ANIMAL SPECIES
V. Perri, O. Be11uzzi, C. Biondi, P.G. Borasio,
97
109
A. Capuzzo, M.E. Ferretti & A. Trevisani 119
QUESTIONS RAISED BY THE ELECTRON MICROCOPIC LOCALIZATION OF ACETYLCHOLINESTERASE AND BUTYRYLCHOLINESTERASE IN NORMAL AND DENERVATED SUPERIOR CERVICAL GANGLIA IN THE CAT
G.B. Koelle, R. Davis, W.A. Koelle, G.A. Ruch, K.K. Rickard & U.J. Sanville 127
ACETYLCHOLINE METABOLISM IN PC12, A CLONAL CELL LINE ON SECRETORY CELLS
B.D. Howard & W.P. Me1ega
REGULATION OF CHOLINERGIC TRANSMISSION IN ADRENAL HEDULLA
E. Costa, A. Guidotti, I. Hanbauer, T. Hexum, L. Saiani & H.~Y. T. Yang
EFFECT OF LATRODECTUS MACTANS TREDECIMGUTTATUS VENOM ON SYNAPTIC TRANSMISSION OF CHICKEN CILIARY GANGLION IN VITRO
L. Bo1zoni, A. Meneguz & P. Paggi
133
143
155
CONTENTS
PERIPHERAL CHOLINERGIC SYNAPSES: HEART, MYENTERIC PLEXUS AND NEUROMUSCULAR FUNCTION
REGULATION OF ACETYLCHOLINE SYNTHESIS AND RELEASE IN THE ISOLATED HEART
K. Loffelholz, R. Lindmar & W. Weide
MODULATION BY SCOPOLAMINE, ACETYLCHOLINE AND CHOLINE OF THE EVOKED RELEASE OF ACETYLCHOLINE FROM THE GUINEA PIG MYENTERIC PLEXUS: EVIDENCE FOR A MUSCARINIC FEEDBACK INHIBITION OF ACETYLCHOLINE SECRETION
H. Kilbinger, R. Kruel & I. Wessler
KINETIC STUDIES ON THE RELEASE OF [3H]-ACETYLCHOLINE FROM GUINEA PIG MYENTERIC PLEXUS: DIFFERENCE IN THE EFFECTS OF MORPHINE AND REDUCED CALCIUM INFLUX
J.C. Szerb
Na+-K+-ACTIVATED ATPase AND NON-QUANTAL/CYTOPLASMIC RELEASE OF ACETYLCHOLINE
E.S. Vizi
HYDROLYSIS OF ACETYLCHOLINE BY FROG SKELETAL MUSCLE
R. Miledi, P.C. Molenaar & R.L. Polak
EARLY EFFECTS OF DENERVATION ON ACETYLCHOLINE A~~ CHOLINE ACETYLTRANSFERASE IN SKELETAL MUSCLE
R. Miledi, P.C. Molenaar & R.L. Polak
RELEASE OF ACETYLCHOLINE TRIGGERED BY THE VENOM OF GLYCERA CONVOLUTA
R. Manaranche, M. Thieffry & M. Israel
ELECTROPHYSIOLOGICAL AND MORPHOLOGICAL CORRELATES OF THE RE-INNERVATION OF RAT NEUROMUSCULAR JUNCTION: IMPLICATIONS ON THE ROLE OF MEMBRANE COMPONENTS SUCH AS GANGLIOSIDES IN THE MOTOR NERVE SPROUTING
A. Gorio, G. Carmignoto, M. Finesso, A. Leon, P. Marini, L. Tredese & R. Zanoni
xi
159
169
177
187
197
205
215
221
xii CONTENTS
ISOLATION OF SYNAPTIC VESICLES FROM THE MYENTERIC PLEXUS OF GUINEA PIG
G.H.C. Dowe, H. Kilbinger & V.P. Whittaker
PERIPHERAL CHOLINERGIC SYNAPSE: PRESYNAPTIC MECHANISMS
THE STRUCTURE OF CHOLINERGIC SYNAPTIC VESICLES
H. Stadler
INHIBITION OF MEMBRANE TRANSPORT SYSTEMS IN SYNAPTOSOMES FROM TORPEDO ELECTRIC ORGAN BY SNAKE NEUROTOXINS
M.J. Dowdall & P. Fretten
BIOCHEMICAL AND BIOPHYSICAL ASPECTS OF STIMULATION INDUCED VESICLE HETEROGENEITY IN CHOLINERGIC SYNAPTIC VESICLES
P.E. Giompres, H. Zimmermann & V.P. Whittaker
ACETYLCHOLINE STORAGE AND CALCIUM CLEARANCE BY SYNAPTIC VESICLES
M. Israel
ACETYLCHOLINE CHANGES DURING TRANSMISSION OF A SINGLE NERVE IMPULSE
Y. Dunant, J. Corthay, L. Eder & F. Loctin
UPTAKE OF ACETYLCHOLINE INTO TORPEDO SYNAPTIC VESICLES IN VITRO
Y.A. Luqmani & P. Giompres
A VESICULAR SITE OF ORIGIN FOR THE RELEASE OF A CHOLINERGIC FALSE TRANSMITTER AT THE TORPEDO SYNAPSE
Y.A. Luqmani & V. P. Whittaker
TRANSMEMBRANE POTENTIAL AND CATION DIFFUSION GRADIENTS IN ISOLATED CHOLINERGIC SYNAPTIC VESICLES: POSSIBLE MODEL FOR ENERGIZATION OF VESICULAR ACETYLCHOLINE UPTAKE
J.B. Suszkiw
235
241
249
261
273
287
301
307
313
CONTENTS
INCORPORATION OF ACETATE INTO ACETYLCHOLINE AND OTHER COMPOUNDS IN THE TORPEDO ELECTRIC ORGAN
J. Corthay, F. Loctin & Y. Dunant
PERIPHERAL CHOLINERGIC SYNAPSE: POSTSYNAPTIC ASPECTS
CHOLINERGIC RECEPTOR ISOLATION
xiii
321
W.H. Hopff, A.A. Hofmann, G. Riggio & P.G. Waser 323
NEW EVIDENCE FOR TRUE IMMUNOPHARMACOLOGIC BLOCKADE IN MYASTHENIA GRAVIS
A.K. Lefvert, S. Cuenoud & B.W. Fu1pius
IMMUNOHISTOCHEMICAL DEMONSTRATION OF IgG AND Fab FRAGMENTS AT MOTOR ENDPLATES OF PASSIVELY TRANSFERRED MICE
B. Lowenad1er, E. Hei1bronn & K. Toyka
ON THE EFFECTS OF ANTICHOLINERGIC AGENTS ON MUSCARINIC RECEPTORS OF DIFFERENT LOCALIZATION
D.A. Kharkevich, A.P. Sko1dinov, D.N. Samoi1ov
333
343
& V.A. Shorr 351
PERIPHERAL CHOLINERGIC SYNAPSE: AXONAL ASPECTS
LIGAND INTERACTIONS OF AXONAL MEMBRANES
H.C. Mautner, J.E. Jumb1att & J.K. Marquis
AXONAL TRANSPORT OF PHOSPHOGLYCERIDES TO CHOLINERGIC SYNAPSES
B. Droz, M. Brunetti, L. di Giamberardino, H.L. Koenig & G. Porce11ati
ACETYLCHOLINESTERASE AND BUTYRYLCHOLINESTERASE: SIMILARITIES IN NORMAL AND DENERVATED MUSCLES, DIFFERENCES IN AXONAL TRANSPORT
L. di Giamberardino .& J. Y. Couraud
367
377
387
xiv CONTENTS
CENTRAL CHOLINERGIC SYNAPSE: PRECURSORS FOR ACETYLCHOLINE SYNTHESIS
THE ACTIVITY OF GLYCEROPHOSPHOCHOLINE PHOSPHODIESTERASE IN BRAIN TISSUE
G.B. Ansell & S. Spanner
SYNTHESIS OF CHOLINE IN THE BRAIN
H. Kewitz & O. P1eu1
ORIGIN OF ACETYL GROUPS OF ACETYLCHOLINE IN THE BRAIN AND THE ROLE OF ACETYLCOENZYME A IN THE CONTROL OF ITS SYNTHESIS
S. Tucek, V. Dolezal & J. Ricny
CHOLINE AVAILABILITY AND THE SYNTHESIS OF ACETYLCHOLINE
D.R. Haubrich, N.H. Gerber, A.B. Pflueger & W.J. Pouch
ACETYLCHOLINE SYNTHESIS AND GLUCOSE OXIDATION WITH VARIOUS OXYGEN ~EVELS IN VIVO AND IN VITRO
G.E. Gibson, H.J. Ksiezak & T.E. Duffy
REGULATION OF ACETYLCHOLINE RELEASE DURING INCREASED NEURONAL ACTIVITY
L. Wecker & A.M. Goldberg
THE UPTAKE AND ACETYLATION OF 3H-CHOLINE IN BRAIN OF INBRED STRAINS OF MICE
R. Reynolds & A.K. Prince
LEAST SQUARES ANALYSES OF THE KINETICS OF CHOLINE UPTAKE IN RAT BRAIN SYNAPTOSOMES
A.M. Kotas & A.K. Prince
393
405
415
425
443
451
463
469
CONTENTS
CENTRAL CHOLINERGIC SYNAPSE: SYNAPTOSOMES AND BRAIN SLICES
INFLUX AND EFFLUX OF N.N.N-TRIMETHYL-N-PROP-2-YNYLAMMONIUM BY A RAT BRAIN SYNAPTOSOME PREPARATION
L.A. Barker
INTERACTION OF CHOLINE TRANSPORT WITH ACETYLCHOLINE RELEASE AND SYNTHESIS
R.M. Marchbanks
CHOLINE TRANSPORT AND THE REGULATION OF ACETYLCHOLINE SYNTHESIS IN SYNAPTOSOMES
R.S. Jope & D.J. Jenden
CHOLINE UPTAKE IN NERVE CULTURES AND IN SYNAPTOSOMAL PREPARATION IS REGULATED BY THE ENDOGENOUS POOL OF CHOLINE
R. Massarelli & T.Y. Wong
INTERRELATIONSHIP BETWEEN ACETYLCHOLINE RELEASE FROM SYNAPTOSOMES AND Na-K ATPase ACTIVITY
J.R. Cooper & E.M. Meyer
ACETYLCHOLINE METABOLISM IN RAT NEOSTRIATAL SLICES
xv
475
489
497
511
521
M.H. Weiler, D.J. Jenden. I.J. Bak & U. Misgeld 531
CENTRAL CHOLINERGIC SYNAPSE: CHOLINERGIC MECHANISMS IN THE EYE
THE CHOLINERGIC SYSTEMS OF THE EYE
T.W. Mittag
LIGHT EVOKED RELEASE OF ACETYLCHOLINE FROM THE RABBIT RETINA IN VIVO
M.J. Neal & S.C. Massey
BIOCHEMICAL AND PUPILLOGRAPHIC STUDIES OF GUINEA PIG IRIS DURING ACETYLCHOLINESTERASE INHIBITION
F. Fonnurn, N.E. S~li, P.K. Opstad, M. Opsahl & R. Lund-Karlsen
541
555
569
xvi CONTENTS
ACETYLCHOLINE RECEPTORS IN THE CENTRAL NERVOUS SYSTEM
ON THE IONIC MECHANISM OF PRESYNAPTIC MUSCARINIC RECEPTOR ACTION IN RAT HIPPOCAMPUS
O. Nordstrom, A. West1ind, B. Hedlund, A. Unden & T. Bartfai 579
MUSCARINIC CHOLINERGIC RECEPTOR LOCALIZATION BY RADIOHISTOCHEMISTRY
J.K. Wamsley, M.A. Zarbin, N.J.M. Birdsall & M.J. Kuhar
"BINDING STATES" OF MUSCARINIC RECEPTORS
N.J.M. Birdsall, C.P. Berrie, A.S.V. Burgen, R. Hammer, E.C. Hulme & J. Stockton
INVESTIGATION ON THE EFFECT OF CHOLINERGIC AGONISTS AND ANTAGONISTS ON CYCLIC NUCLEOTIDE LEVELS IN VIVO: EFFECT OF LYSO-PHOSPHATIDYLSERINE
S. Teo1ato, G. Ca1derini, A.C. Bonetti, A. Battiste11a & G. Toffano
REGULATION OF MUSCARINIC RECEPTOR BINDING
F.J. Ehlert, W.R. Roeske & H.I. Yamamura
STRUCTURAL AND STERIC ASPECTS OF COMPOUNDS RELATED TO OXOTREMORINE
R. Dah1bom
SEARCH FOR NICOTINE-LIKE RECEPTOR BINDING SITES IN BRAIN
A. Nordberg & C. Larsson
IONIC EFFECTS ON ANTAGONIST BINDING TO THE MUSCARINIC RECEPTOR
B. Hedlund
STUDIES ON THE STRUCTURE OF ACETYLCHOLINE RECEPTOR
V,. Witzemann & J .H. Walker
587
595
601
609
621
639
647
653
xvii CONTENTS
NEWLY SYNTHESIZED ACETYLCHOLINE RECEPTOR IN DENERVATED SKELETAL MUSCLE
M.G. Giacobini-Robecchi & M. Garelli
CENTRAL CHOLINERGIC PATHWAYS
ANATOMICAL ORGANIZATION OF SOME CHOLINERGIC SYSTEMS IN THE MAMMALIAN FOREBRAIN
H.C. Fibiger & J. Lehmann
CHOLINERGIC PATHWAYS TO THE CEREBRAL CORTEX IN RATS
H. Wenk, V. Bigl, U. Meyer & D. Biesold
LESIONS OF THE GLOBUS PALLIDUS: CHANGES IN CORTICAL CHOLINE ACETYL TRANSFERASE , CHOLINE UPTAKE AND ACETYLCHOLINE OUTPUT IN THE RAT
F. Casamenti, F. Pedata, S. Sorbi, G. Lo Conte
659
663
673
& G. Pepeu 685
MAPPING OF CHOLINERGIC SYSTEMS IN ROSTRAL FOREBRAIN OF THE RODENT
H. Kimura, P.L. McGeer, J.H. Peng & E.G. McGeer 695
INTERACTIONS BETWEEN DIFFERENT NEUROTRANSMITTER SYSTEMS
REGULATION OF SEPTAL-HIPPOCAMPAL CHOLINERGIC NEURONS BY CATECHOLAMINES
S.E. Robinson, D.L. Cheney & E. Costa
INTERACTIONS OF NEUROPEPTIDES WITH CHOLINERGIC SEPTALHIPPOCAMPAL PATHWAY: INDICATION FOR A POSSIBLE TRANS-SYNAPTIC REGULATION
P.L. Wood, D.L. Cheney & E. Costa
CHOLINERGIC-MONOAMINERGIC INTERACTIONS IN SELECTED REGIONS OF THE BRAIN: HISTOCHEMICAL AND PHARMACOLOGIC ANALYSES
L.L. Butcher, N.J. Woolf, A. Albanese & S.H. Butcher
705
715
723
xviii CONTENTS
ON MODULATION OF CEREBRAL CHOLINERGIC MECHANISMS BY ENDOGENOUS INDOLEAMINES AND THEIR DERIVATIVES
B. Oderfe1d-Nowak & M.H. Aprison
INFLUENCE OF GABA ON ACETYLCHOLINE RELEASE FROM THE GUINEA PIG BRAIN
L. Beani, C. Bianchi & S. Tangane11i
GABA-ACETYLCHOLINE INTERACTION IN THE RAT STRAITUM
B. Scatton & G. Bartho1ini
REGULATION OF CHOLINERGIC ACTIVITY IN THE RAT HIPPOCAMPUS: IN VIVO EFFECTS OF OXOTREMORINE AND FENFLURAMINE
H. Ladinsky, S. Consolo, A.S. Tire11i, G.L. For1oni
739
763
771
& M. Segal 781
ACETYLCHOLINE, BEHAVIOR AND DRUGS
ACETYLCHOLINE INDUCED ANTINOCICEPTION: COMPARISONS TO OPIATE ANALGESIA
N.W. Pedigo & W.L. Dewey
CHRONIC BARBITAL TREATMENT AND CHOLINERGIC MECHANISMS IN BRAIN
A. Nordberg & G. Wahlstrom
INTERACTION BETWEEN ATROPINE AND HEXOBARBITAL IN THE ABSTINENCE AFTER CHRONIC BARBITAL TREATMENTS IN THE RAT
G. Wahlstrom & A. Nordberg
MARIJUANA AND CHOLINERGIC DYNAMICS
D.L. Cheney, A.V. Revue1ta & E. Costa
ANTINOCICEPTIVE ACTION OF CHOLINOMIMETICS EVALUATED WITH THE METHOD OF THE RETURN OF CORNEAL ANESTHESIA INDUCED WITH PROCAINE
F. Aloisi, A. Scotti de Caro1is & V.G. Longo
795
809
819
825
833
CONTENTS
DO GANGLIOSIDES AFFECT THE RECOVERY OF CHOLINERGIC ENZYMES OF RATS AFTER SEPTAL LESIONS?
M. Wojcik & J. Ulas
COMPARA~IVE STUDIES ON RAT BRAIN SOLUBLE ACETYLCHOLINESTERASE AND ITS MOLECULAR FORMS DURING INTOXICATION BY DFP AND PARAOXON
H. Michalek, G.M. Bisso & A. Meneguz
CLINICAL SIGNIFICANCE OF CHOLINERGIC MECHANISMS
BASIC PHENOMENA UNDERLYING NOVEL USE OF CHOLINERGIC AGENTS, 'ANTICHOLINESTERASES AND PRECURSORS IN NEUROLOGICAL INCLUDING PERIPHERAL AND PSYCHIATRIC DISEASE
A.G. Karczmar
CLINICAL TRIALS WITH CHOLINE AND 4-AMINOPYRIDINE IN HUNTINGTON'S CHOREA
S.M. Aquilonius & S.A. Eckernas
PHARMACOKINETICS OF NEOSTIGMINE AND PYRIDOSTIGMINE IN MAN AND ITS CORRELATION TO CLINICAL EFFECTS IN MYASTHENIA GRAVIS
S~A. Eckernas, S.M. Aquilonius, P. Hartvig, B. Lindstrom, P.O. Osterman & E. Stalberg
RED BLOOD CELL/PLASMA CHOLINE RATIO - A POSSIBLE BIOLOGICAL MARKER OF LITHIUM THERAPY - CLINICAL CORRELATIONS AND LIMITATIONS
E.F. Domino, B. Mathews, S.K. Tait, S.K. Demetriou
xix
841
847
853
871
879
& F. Fucek 891
BLOOD CHOLINE AND ITS MEANING IN PSYCHIATRIC AND NEUROLOGIC DISEASE STATES
I. Hanin, D.G. Spiker, A.G. Mallinger, U. Kopp, J.M. Himmelhoch, J.F. Neil & D.J. Kupfer 901
CHOLINERGIC DYSFUNCTION: A COMMON DENOMINATOR IN METABOLIC ENCEPHALOPATHIES
J.P. Blass, G.E. Gibson, T.E. Duffy & F. Plum 921
xx CONTENTS
CHOLINOMIMETIC AGENTS AND HUMAN MEMORY: PRELIMINARY OBSERVATIONS IN ALZHEIMER'S DISEASE
K.L. Davis, R.C. Mohs, B.M. Davis, G.S. Rosenberg, T.H. Horvath & Y. DeNigris 929
EFFECTS OF LECITHIN ON MEMORY AND PLASMA CHOLINE LEVELS: A STUDY IN NORMAL VOLUNTEERS
J.C. Gillin, N Sitaram, H. Weingartner, C. Crammer & I. Hanin
HYPERSENSITIVE CHOLINERGIC FUNCTIONING IN PRIMARY AFFECTIVE ILLNESS
N. Sitaram, A.M. Moore, C. Vanskiver, J. Blendy,
937
J.I. Nurnberger, Jr., E.S. Gershon & J.C. Gillin 947
PARTICIPANT LIST 963
CONTRIBUTOR INDEX 973
SUBJECT INDEX 977